Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Aims/hypothesis: Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. Methods: In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45mg daily during 6weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Results: Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Conclusions/interpretation: Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones. Trial registration:: ClinicalTrial.gov NCT01090752 Funding:: Hypertension Research Foundation Lausann

Persistence of Resistant Staphylococcus epidermidis after Single Course of Clarithromycin

Short course of antimicrobial therapy can select resistant bacteria that persist for 4 years or longer

Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture

The role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria. complex).Vitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, β-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain.We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity

Resveratrol Increases Glucose Induced GLP-1 Secretion in Mice: A Mechanism which Contributes to the Glycemic Control

Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo

Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli

Significant differential gene duplication without ancestral tetraploidy in a genus of mexican fish

A comparison of the protein products of 20–25 structural gene loci among the known species of the goodeid fish genus Skiffia suggests that at least 4 loci (16–20%) have undergone species-specific duplications (or, in 1 case, apparent loss) during the evolution of the genus. The species are clearly diploids, and the data therefore indicate that even a large proportion of differentially duplicated loci within a group of related fish species is not critical evidence of common tetraploid ancestry. Differential duplication of structural gene loci may be an important component of the genetic differences that separate congeneric conventional diploid species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42725/1/18_2005_Article_BF01953797.pd

Knowledge and awareness of the general public and perception of pharmacists about antibiotic resistance

Background Antibiotic resistance (AR) continues to be a serious problem. Many factors contribute to AR, including inappropriate use of antibiotics, in which both healthcare professionals and patients play a contributing role. This study aimed to assess the awareness and knowledge of antibiotic usage and AR among the general public (in affluent and deprived areas) and community pharmacists' (CPs') in Greater London. Methods A cross-sectional survey involving members of the public was conducted between July 2014 and February 2015. Stage one involved members of the public (N = 384) residing in affluent areas of London. The second stage targeted public (N = 384) in deprived areas of London. In addition, CPs (N = 240) across the same areas were also surveyed. Data analysis was performed using Microsoft Excel and SPSS Software packages. Results Response rate: 36% (n = 139/384) and 57% (n = 220/384) and 25% (n = 60/240) of public residing in affluent areas, deprived areas and of CPs respectively was achieved. Definitive trends in knowledge of how antibiotics work could not be drawn to distinguish between affluent and deprived areas. However, public respondents residing in affluent areas possessed better understanding of AR and prudent use of antibiotics, and this was statistically significant in both cases (p < 0.05). Exposure to an antibiotic campaign (32% in affluent areas, 17% in deprived areas) did not raise public respondents' knowledge on AR and only partially raised their general knowledge on antibiotics usage. Only 20% of public residing in deprived areas received counselling from a CP, among them 74% had an antibiotic prescribed on at least one previous occasion. Those who received counselling displayed better knowledge about concordance/adherence with respect to antibiotic usage (p < 0.05) whereas exposure to an antibiotic campaign made no significant impact on knowledge about concordance/adherence. Conclusion The study highlights that there has been no change in the status quo with respect to awareness of antibiotic usage and AR even after the implementation of several awareness campaigns in England. Those who benefited from CP counselling showed a significant better knowledge towards prudent antibiotic usage which stresses the importance of CPs' counselling on antibiotic prescription